title: Design of metastable β-sheet oligomers from natively unstructured peptide.
abstract: Amyloid oligomers represent the primary pathological species for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Toxic oligomers are formed by many different proteins and peptides, but their polydispersity makes them highly dynamic and heterogeneous. One way to stabilize these structures is to prepare constrained peptides that can be used to study amyloid intermediates, to identify oligomer-specific drugs, and to generate conformational antibodies. These conformational antibodies have demonstrated that oligomers share a common epitope. In this research, we used a 40-amino acid unstructured segment of prion protein (Prp) 109-148 with substitutions of methionine for glycine (Prp-G) residues to prepare a stable and homogeneous population of β-sheet oligomer mimics. These structures were characterized by multiple biophysical and biochemical techniques that show characteristic features of oligomers. Finally, this preparation was not detected by three different sequence dependent prion antibodies.
authors.affiliation: Department of Neurology, the George P. and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, ‡Departments of Biochemistry and Molecular Biology, the Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Guerrero-Muñoz
authors.forename: Diana L
authors.initials: DL
authors.lastname: Castillo-Carranza
authors.forename: Urmi
authors.initials: U
authors.lastname: Sengupta
authors.forename: Mark A
authors.initials: MA
authors.lastname: White
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
mesh_terms: D000595:Amino Acid Sequence; D058227:Amyloidogenic Proteins / Q000737:chemistry*; D032701:Biomimetics / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D058227:Amyloidogenic Proteins; D010455:Peptides; D011328:Prions